The trigeminal nerve mediates pain sensation from craniofacial tissues including specialized structures such as the teeth, dura, and cornea. Pain that occurs during toothache, headache, and dry eye syndrome is a prevalent health problem, arises from varied etiology and often is difficult to manage. In addition to sensation, other aspects of pain (autonomic/endocrine reflexes, endogenous pain controls) can be altered by persistent trigeminal pain conditions. This proposal uses neurophysiological methods to test the central hypothesis that distinct groups of brainstem neurons mediate different aspects of corneal pain and that these neurons can be identified by their encoding properties, response to analgesic drugs, and efferent projection status. Specific Aim 1 defines the properties of trigeminal brainstem neurons that encode different corneal stimulus modalities (chemical, mechanical, cold). Corneal units that project to the sensory thalamus or superior salivatory nucleus/facial nucleus region are presumed to serve a role in sensory-discriminative or reflex autonomic/somatomotor functions, respectively. Specific Aims 2 and 3 assess the role of the longitudinal fiber system that connects rostral and caudal portions of trigeminal subnucleus caudalis in different aspects of cornea pain processing. Specific Aim 4 tests the hypothesis that receptors for glutamate mediate corneal input to trigeminal subnucleus caudalis and are necessary for the modulation of evoked activity seen after morphine. Specific Aim 5 tests the hypothesis that mu opioid agonists such as morphine act at sites outside the trigeminal brainstem complex to enhance corneal units at rostral portions of subnucleus caudalis and inhibit corneal units at the most caudal portions of subnucleus caudalis. These results will provide new information on the properties of trigeminal neurons that mediate the sensory-discriminative and ocular-specific reflex aspects of corneal pain and will lead to a better understanding of the brainstem organization that underlies craniofacial pain processing.